This is a renewal of the Joseph and Kathleen Bryan Alzheimer's Disease Research Center (Bryan ADRC), Allen D. Roses, Principal Investigator, at Duke University which wa initially funded in September 1985. The overall specific aims of the Bryan ADRC continue to be the identification and cloning of the genetic locus (loci) responsible for the development of late onset and early onset Alzheimer's Disease; and the design and testing of rational treatment to prevent or significantly delay expression of the disease. The research strategy is clinically based and uses several methods of genetic linkage analyses and molecular genetic techniques. Research projects are highly interactive with NIA grant number AG07922, "Genetics of Late and Early Onset Alzheimer's Disease" (LEAD Award), Allen D. Roses, PI. Intensive study of familial AD designed to determine the earliest manifestations of AD includes those family members who are not symptomatic but estimated to be at high risk. The LEAD Award is aimed at defining the genetic loci directly. Neuropsychologic (Project 1, Welsh, PI), neuroradiologic (Project 2, Hoffman, PI), and clinical neurophysiologic tests (Project 3, Schiffman, PI) are included in this Center renewal. Also included are projects involving testing and development of new methods of linkage analyses that can utilize the molecular genetic linkage data (Project 4, Dawson, PI), and psychiatric (Project 5, Breitner, PI) and neuropathologic evaluations (Project 5, Crain, PI) that are highly interactive with the Rapid Autopsy Protocol and Brain Bank. Study of a newly described prosimian primate model for AD pathology (Project 7, Schmechel, PI) as well as four pilot projects are included. The Bryan ADRC cores, Administrative (Core A), Clinical Research Development (Core B), Neuropathology (Core C), Education Information Transfer (Core D), and the Indiana National Cell Bank (Core E), enable the Center to functionally integrate the clinical, research, education information transfer and resource components.